Characteristics of a Non-Complement-Dependent C3-Reactive Complex Formed From Factors in Nephritic and Normal Serum

Abstract

All immune origin of glomerulonephritis, with complement playing a major role, was first suspected 50 yr ago when it was found that serum complement levels in nephritis were often low. Only recently however, with the identification of individual components, have details of the complement reaction become susceptible to investigation. It is already apparent that there are differences in the way in which complement is involved in nephritis. For example, serum levels of individual components have been shown to be variably reduced depending upon the type of nephritis (1-3). Furthermore, deposition of C3 in the glomeruli occurs in many cases in which C3 and total complement levels have remained normal during the course of the disease (4-6). In other types of nephritis, however, the configuration of C3 deposition correlates well with the supposed target of the immune reaction (4, 5).The participation of complement in producing the type of nephritis designated hypocomplementemic persistent or membranoproliferative is of special interest. In this disease CHs0 and C3 may remain at very low levels over long periods (6, 7) and C3 is usually found in the glomerular capillary walls by immunofluorescent techniques, often without the presence of identifiable IgG. 1 The persistently reduced serum levels of C3 have been explained by some as the result of diminished synthesis of C3 (8) and ascribed by others to an ongoing complement reaction in the glomeruli in which C3 is continuously being broken down (9). Recent observations suggest that a site of complement breakdown may be circulating plasma. Inactivators of guinea pig (10) and human (11) complement have been found in the serum of patients with acute, chronic hypocomplementemic, and lupus nephritis, and in a previous communication from this ]nboratory, Spitzer et al. (12) reported the presence of a factor in the

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis

“…An alternative reaction sequence to that given above in which cofactor is an enzyme-inhibitor complex and C3NeF is an antagonist of the inhibitor which is generated in the nephritic patient, has been discussed elsewhere (23).…”

“…The measurement of C3NeF in the hypocomplementemic serum was based on the ability of the serum to break down the C3 contained in normal human serum under standard conditions. Details of this reaction have been described earlier (23). In brief, the amount of C3 breakdown was quantitated by measurement of the loss of the B antigenic determinant of C3 after incubation of mixtures of 0.1 ml of the patient's serum and 0.3 ml of normal human serum for 20 min at 370C.…”

Properdin and C3 Proactivator: Alternate Pathway Components in Human Glomerulonephritis

“…A C3 nephritic factor (C3 Nef) has been described in patients with CMPGN which activated C3 to PiA and a2D in the presence of cofactor and magnesium (28). C3 nephritic factor is not C3PA but apparently requires C3PA for C3 activation (29 (Table IV).…”

Hypocomplementemia of Membranoproliferative Nephritis DEPENDENCE OF THE NEPHRITIC FACTOR REACTION ON PROPERDIN FACTOR B

“…The postulated reaction sequence was as follows (4,5) Since C3 is the primary target of the C3 nephritic factor, the complement profile of patients with MPGN is distinctive and differs from that seen when immune complexes are added to NHS in vitro (8). In the latter instance, C3 convertase is formed from the early reacting components and all nine components are consumed to some degree.…”